Investigations into the molecular targets of neuroleptic drugs and their associated intracellular signaling pathways have yielded a wealth of information regardingthe cellular perturbations associatedwith schi/ophrenia. The combined studies outlined in Projects 1-5 will extend upon this existing knowledge with rigorouscell biological, molecular, biochemical,behavioral, and electrophysiological studies of neuronal cells upon neuroleptic drug treatment These studies have the potential to provide greater insights into the etiology of schi/ophrenia as well as lo make possible novel and/or more efficient neuroleptic drug treatment. The Transgcnic Animal Core will be a center devoted to facilitating those experiments proposed in Projects 1-5 thai require the use of genetically modified animals.The experimentsoutlined in these Projects require the creation and maintenance of large numbersof genetically modified animals; it will be the responsibility of tie Core to produce these transgenic, knockout, and knockin animalsin an efficient, timely, and cost-effective manner. The existence of a centralized facility staffed with experienced personnel will ensure that this is feasible. In order to produce lurge numbers of transgenic animalsefficiently, Specific Aim I of the Core will be the production of BACs carrying transgenes. The Core will then use these modified BACs in Specific Aim II, the production of transgenic and knockout mouse lines and the testing of these lines. Upon production of transgenic and conditional knockout animals, the Core will test and characterize these animals to validatethem for use in the proposed studies, l-'inally, Specific Aim III of the Core will be the breeding and maintenance of these and other mouse lines (hat will be used throughout the studies in Projects 1-5.